Institutional Repository of Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences
| Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed | |
| Liu Changshui1,2; Zang Kun1,2,3; Li Shihao1,2,3,4; Li Fuhua1,2,3,4; Ma Qingiun1,2,3,4 | |
| 2020-02-15 | |
| Source Publication | JOURNAL OF OCEANOLOGY AND LIMNOLOGY
 |
| ISSN | 2096-5508 |
| Pages | 9 |
| Corresponding Author | Ma Qingiun(qma@qdio.ac.cn) |
| Abstract | Thymidylate synthase (TS) is a key enzyme in the de novo biosynthesis of thymidine monophosphate, serving as a well-known drug target in chemotherapy against cancers and infectious diseases. Additional to its clinical value, TS is supposed to be a promising drug target in aquatic-disease control. To facilitate designing pathogen-specific TS inhibitors for shrimp-disease control, we report the crystal structures of TS from Litopenaeus vannamei (LvTS) in the apo form, LvTS-dUMP complex and LvTS-dUMP-raltitrexed complex at 2.27 A, 1.54 A, and 1.56 A resolution, respectively. LvTS shares a similar fold with known TSs, existing as a dimer in the crystal. The apo LvTS and LvTS-dUMP take an open conformation, and raltitrexed binding induces structural changes into a closed conformation in LvTS-dUMP-raltitrexed. Compared to those in other known TS-dUMP-raltitrexed complexes with the closed conformation, the C-terminal loop in LvTS-dUMP-raltitrexed shifts its position away from the bound raltitrexed; the distance between C6 of dUMP and S gamma of the catalytic cysteine is obviously longer than that in the known TS structures with closed conformations, resembling that in the TS structures with open conformations. Other species-specific interactions with dUMP and raltitrexed are also observed. Therefore, LvTS-dUMP-raltitrexed adopts a loosely closed conformation with structural features intermediate between the closed and the open conformations that were reported in other TSs. Our study provides the first crustcean TS structure, and reveals species-specific interactions between TSs and the ligands, which would facilitate designing pathogen-specific TS inhibitors for shrimp-disease control. |
| Keyword | thymidylate synthase (TS) closed conformation deoxyuridine monophosphate (dUMP) thymidine monophosphate (TMP) raltitrexed Litopenaeus vannamei |
| DOI | 10.1007/s00343-019-9184-8 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | National Natural Science Foundation of China[31572660] ; National Natural Science Foundation of China[31872600] ; 1000 Talents Program ; Qingdao Innovation Leadership Project[18-1-2-12-zhc] |
| WOS Research Area | Marine & Freshwater Biology ; Oceanography |
| WOS Subject | Limnology ; Oceanography |
| WOS ID | WOS:000516140400007 |
| Publisher | SCIENCE PRESS |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/165539 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Ma Qingiun |
| Affiliation | 1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266000, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Ctr Ocean Megasci, Qingdao 266071, Peoples R China |
| First Author Affilication | Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences |
| Corresponding Author Affilication | Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences; Center for Ocean Mega-Science, Chinese Academy of Sciences |
| Recommended Citation GB/T 7714 | Liu Changshui,Zang Kun,Li Shihao,et al. Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed[J]. JOURNAL OF OCEANOLOGY AND LIMNOLOGY,2020:9. |
| APA | Liu Changshui,Zang Kun,Li Shihao,Li Fuhua,&Ma Qingiun.(2020).Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed.JOURNAL OF OCEANOLOGY AND LIMNOLOGY,9. |
| MLA | Liu Changshui,et al."Structural analysis of a shrimp thymidylate synthase reveals species-specific interactions with dUMP and raltitrexed".JOURNAL OF OCEANOLOGY AND LIMNOLOGY (2020):9. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Structural analysis （1545KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View | |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment